Neurobiology and Anatomy 1

8/14/2019 Neurobiology and Anatomy 1

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NEUROSCIENCE

LECTURE

SUPPLEMENT

Nachum Dafny, Ph.D., Professor

Department of Neurobiology and Anatomy

University of Texas Medical School at Houston

C. Motor System


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TABLE OF CONTENTSPage

Overview of the Motor System................................................................................1

Motor Units and Muscle Receptors .......................................................................12

Spinal Reflexes ......................................................................................................23

Cerebellum.............................................................................................................33

Basal Ganglia.........................................................................................................43

Motor Cortex..........................................................................................................53

Integrated Motor System and Disorders of the Motor System..............................61


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OVERVIEW OF THE MOTOR SYSTEM

James Knierim, Ph.D.

Much of the brain and nervous system is devoted to the processing of sensory input, inorder to construct detailed representations of the external environment. Through vision,audition, somatosensation, and the other senses, we perceive the world and our relationship to it.

This elaborate processing would be of limited value, however, unless we had a way to act upon

the environment that we are sensing, whether that action consist of running away from a

predator; seeking shelter against the rain or wind; searching for food when one is hungry;moving ones lips and vocal cords in order to communicate with others; or performing the

countless other varieties of actions that make up our daily lives. In some cases the relationship

between the sensory input and the motor output are simple and direct; for example, touching ahot stove elicits an immediate withdrawal of the hand (Fig. 1). Usually, however, our conscious

actions require not only sensory input but a host of other cognitive processes that allow us to

choose the most appropriate motor output for the given circumstances. In each case, the finaloutput is a set of commands to certain muscles in the body to exert force against some other

object or forces (e.g., gravity). This entire process falls under the category ofmotor control.

Some Necessary Components of Proper Motor Control

(1) Volition. The motor system must generate movements that are adaptive and that

accomplish the goals of the organism. These goals are evaluated and set by high-order areas of

the brain, including the prefrontal cortex. The motor system must transform these goals anddesired movements into the appropriate activations of muscles to perform the desired activity.

(2) Coordination of signals to many muscle groups. Few movements are restricted tothe activation of a single muscle. Rather, most movements result from the coordinated activityof different muscle groups. The act of moving your hand from inside your pocket to a position

in front of you requires the coordinated activity of the shoulder, elbow, and wrist. Making the

same movement while removing a 10-lb weight from your pocket may result in the sametrajectory of your hand, but will require different sets of forces on the muscles that make the

movement. The task of the motor system is to determine the necessary forces and coordination

at each joint in order to produce the final, smooth motion of the arm.

Cognition

Action

ENVIRONMENT

Senses

Fig. 1. Sensory receptors provide information about the

environment, which is then used to produce action to change

the environment. Sometimes the pathway from sensation to

action is direct, as in a reflex. In most cases, however,

cognitive processing occurs to make actions adaptive and

appropriate for the particular situation.


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(3) Proprioception. In order to make a desired movement (e.g., raising your hand to ask

a question), it is essential for the motor system to know the starting position of the hand. Raising

ones hand from a resting position on a desk, compared to a resting position on top of the head,results in the same final position of the arm, but these two movements require a very different

pattern of muscle activation. The motor system has a set of sensory inputs (calledproprioceptors) that inform it of the length of muscles and the forces being applied to them; ituses this information to calculate joint position and other variables necessary to make the

appropriate movement.

(4) Postural adjustments. In addition to the coordination of muscles necessary toproduce the desired output, the motor system must also constantly produce adjustments to the

bodys posture in order to compensate for the changes in the bodys center of mass as we move

our limbs, head, and torso. Without these automatic adjustments, the simple act of reaching for acup would cause us to fall forward, as the bodys center of mass shifts to a location in front of

the body axis.

(5) Sensory feedback. In addition to the use of proprioception to sense the position of

the body before a movement, the motor system must use other sensory information in order to

perform the movement accurately. By comparing desired activity with actual activity, sensory

feedback allows for corrections in movements as they take place, and it also allowsmodifications to motor programs so that future movements are performed more accurately.

(6) Compensation for the physical characteristics of the body and muscles. To exerta defined force on an object, it is not sufficient to know only the characteristics of the object

(e.g., its mass, size, etc.). The motor system must also account for the physical characteristics ofthe body and muscles themselves. The bones and muscles have mass that must be considered

when moving a joint, and the muscles themselves have a certain degree of resistance to

movement.

(7) Unconscious processing. The motor system must perform many procedures in an

automatic fashion, without the need for high-order control. Imagine if walking across the roomrequired thinking about planting the foot at each step, paying attention to the movement of each

muscle in the leg and making sure that the appropriate forces and contraction speeds are taking

place. It would be hard to do anything else but that one task. Yet we can walk, talk, chew gum,

button a shirt, and think about how fascinating neuroscience is, all at the same time. A numberof motor tasks are performed in an automatic fashion that does not require effortful processing

by higher brain areas. Moreover, the motor system must be able to perform a number of tasks of

which the organism is completely unaware. For example, many of the postural adjustments thatthe body makes during movement are performed without our awareness. These unconscious

processes allow higher-order brain areas to concern themselves with broad desires and goals,

rather than low-level implementations of movements.

(8) Adaptability. The motor system must adapt to changing circumstances. For

example, as a child grows and its body changes, different constraints are placed on the motorsystem in terms of the size and mass of bones and muscles. The motor commands that work to


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raise the hand of an infant would fail completely to raise the hand of an adult. The system mustadapt over time to change its output to accomplish the same goals. Furthermore, if the system

were unable to adapt, we would never be able to acquire motor skills, such as playing a piano,

hitting a baseball, or performing microsurgery.

These are some of the many components of the motor system that allow us to performcomplex movements in a seemingly effortless way. The brain has evolved exceedingly complexand sophisticated mechanisms to perform these tasks, and researchers have only scratched the

surface in understanding the principles that underlie the brains control of movement.

Functional Segregation and Hierarchical Organization

The ease with which we make most of our movements belies the enormous sophistication

and complexity of the motor system. If you want to get a cup of coffee, you simply stand up,walk to the coffee pot, and pour yourself a cup. Simple, right? Yet very smart engineers have

spent decades trying to get machines to perform such simple tasks, and the most advanced

robotic systems do not come close to emulating the precision and smoothness of movement,under all types of conditions, that we achieve effortlessly and automatically. How does the brain

do it? Although many of the details are not understood, two broad principles appear to be key

concepts toward understanding motor control:

Functional Segregation. The motor system is divided into a number of different areas

that control different aspects of movement. These areas are located throughout the nervous

system. One of the key questions of research on motor control is to understand the functionalroles played by each area.

Hierarchical Organization. The different areas of the motor system are organized in a

hierarchical fashion. Lower levels of the hierarchy control the nuts and bolts of motor

processing, such as calculating the amount of force generated by a single muscle andcoordinating simple reflexes. Higher levels of the hierarchy calculate the trajectories of whole

limb movements and sequences of movements, and they evaluate the appropriateness of a

particular action given the current environmental context.

Because of the hierarchical nature of the motor system, the higher-order areas can

concern themselves with more global tasks regarding action, such as deciding when to act,

devising an appropriate sequence of actions, and coordinating the activity of many limbs. Theydo not have to program the exact force and velocity of individual muscles, or coordinate

movements with changes in posture; these low-level tasks are performed by the lower levels of

the hierarchy.

The motor system hierarchy consists of the following parts (Fig. 2):

Spinal Cord

Brainstem

Motor Cortex


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Association Cortex Side Loops

o Basal Gangliao Cerebellum

Spinal Cord. The spinal cord is the first (lowest) level of the motor hierarchy (Fig. 3).

(1)The spinal cord is the site of motor neurons. These motor neurons reside in the anteriorhorn of the spinal cord and synapse directly onto muscle fibers. Motor neurons are the

only way in which commands from higher areas can be transmitted to muscle. Damage to

motor neurons results necessarily in paralysis of the muscles that were innervated by

those neurons.(2)The spinal cord contains the circuitry for many reflexes. These spinal reflexes include

the myotatic reflex (also called the stretch reflex or deep tendon reflex), the flexor reflex

(limb withdrawal away from a painful stimulus), and many others discussed in the next 2lectures.

(3)The spinal cord controls many complex actions. The most obvious complex action that iscontrolled by circuitry entirely within the spinal cord is gait. Although higher areas canissue commands to begin walking, the circuitry that actually controls the rhythmic motion

of the legs resides in the spinal cord itself.

(4)The spinal cord is influenced by higher levels of the hierarchy. Although many reflexesand complex actions are controlled by neural circuits within the spinal cord, these circuits

can be influenced in complex ways by higher brain centers. This top-down control isnecessary for ensuring that the low-level circuits within the spinal cord are utilized in an

adaptive manner.

Level 4: Association Cortex

Level 2: Brain Stem

(Red Nucleus, ReticularFormation, Vestibular Nuclei,

Tectum, Pontine Nuclei, Inferior

Level 1: Spinal Cord

Level 3: Motor Cortex

Side Loop 1:Basal Ganglia

(Caudate Nucleus, Putamen,Globus Pallidus, SubstantiaNigra, Subthalamic Nucleus)

Thalamus

(VA,VL,CM)

Side Loop 2:Cerebellum

Fig. 2. Schematicrepresentation of the different

levels and interconnections of

the motor system hierarchy.


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Brainstem. The brainstem is the second level of the motor hierarchy.

(1) Brainstem nuclei that are important for motor control include the red nucleus, thevestibular nuclei, the pontine reticular formation, and the medullary reticular formation.

(2)These nuclei process selected afferent sensory inputs that are used to program and adaptmotor commands. As discussed later, the use of sensory input to guide motor output is a

necessary and ubiquitous feature of motor control.

(3)Brainstem nuclei modulate motor circuits that control posture, eye movements, and headmovements.

Motor cortex. The motor cortex is the third level of the motor hierarchy (Fig. 4).

(1)The motor cortex processes numerous task-related variables to produce the desiredaction. Neurons in the motor cortex then give rise to descending motor commands.

Information encoded in these commands includes which part of the body should move, as

well as the force and direction of the movement.

(2) Motor cortex can be divided broadly into 3 areas: primary motor cortex, premotor

cortex, and the supplementary motor area.(3)Descending pathways from the motor cortex can be divided into two systems:

a. The corticospinal system controls motor neurons and interneurons in the spinalcord.

b. The corticobulbar system controls brainstem nuclei that innervate cranial muscles.

Fig. 3. A motor neuron in the spinal cord.

Fig. 4. The motor cortex, the third level of the

motor system hierarchy, is composed of three

major areas: the primary motor cortex (also

called M1), the premotor cortex, and the

supplementary motor area. Note that thesupplementary motor area extends onto the

medial wall of the cortex.


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Association Cortex. The association cortex is the fourth (highest) level of the motor hierarchy(Fig. 5).

(1) High-level association cortical areas create a frame of reference for directingmovements. This task is largely associated with theposterior parietal cortex. In addition

to other tasks, this brain region calculates transformations of sensory inputs from body-centered (egocentric) coordinates to world-centered (allocentric) coordinates, allowingmovements to be directed to the external world regardless of the current orientation and

position of the body. Lower areas of the hierarchy transform the output of these areas

back to the appropriate egocentric coordinates necessary to generate the proper muscle

output. The posterior parietal cortex is also involved in directing attention to salientobjects in the world.

(2) Association cortex integrates behavior to produce goal-directed action appropriate forthe particular context. These poorly understood functions are largely associated with theprefrontal cortex. Actions that are appropriate in one behavioral context (e.g., giving a

hard slap on the back to congratulate a basketball player who just made a critical 3-

pointer) may be completely inappropriate in another context (e.g., giving the same hardslap to ones grandmother to celebrate her 80th birthday). This type of processing,

although not traditionally motor processingper se, is important for producing movements

that are behaviorally adaptive.

Side loops. Two important brain regions are not part of the motor hierarchy, but they influence

the motor cortex profoundly through their connections with the motor thalamus.

(1)Basal ganglia. The basal ganglia comprise a number of distinct forebrain structures thatact as an integrative center for motor output. Damage to the basal ganglia produces

deficits of motor planning, speed of movement, and the ability to enable certainstereotyped motor programs. Parkinsons disease is the most well-known of basalganglia disorders.

(2)Cerebellum. The cerebellum modulates the activity of brainstem nuclei (through directconnections) as well as motor cortex (through its thalamic connections). The cerebellumis important for fine control and timing of movements; it is thought to be necessary for

motor learning (i.e., learning the precise patterns of movement necessary to achieve fine

Fig. 5. The fourth level of the motor

system hierarchy is the association

cortex, primarily the posterior

parietal cortex and the prefrontal

cortex.


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Open Loop System with No Sensory Input. Before describing the role of sensory

input, it is useful to describe the properties of a control system without such input. A system in

which there is no sensory feedback into the system is termed an open loop control system. Insuch a system, a desired output is fed into a controller circuit, which in turns directs the effector

machinery (e.g., robotic arm, biceps muscle, etc.) to produce the output (Fig. 7). In this type ofsystem, there is no role of sensory information to direct, guide, or modulate the output;movements are ballistic and, once initiated, cannot be modified. Such a system is rarely present

in a biological motor system. A nonbiological example would be a timer-controlled

heating/cooling system. In order to cool a room to a desired temperature, a control circuit with a

timer would turn on the air conditioner for a preset amount of time. Once the timer was set,however, there would be no way to keep the air conditioner on longer if the desired temperature

was not reached, or to turn on the heater if the air conditioner made the room too cold. Perhaps

one of the few examples of a biological realistic example of such a ballistic system would be areflexive drop to the ground to avoid an incoming object.

CONTROLLER EFFECTORDESIREDOUTPUT

OUTPUT

Fig. 7. An open loop control system.

Closed Loop System with Feedback Control. An improvement on an open loop

control system is to incorporate sensory information during the execution of a task in order to

improve accuracy. One method of accomplishing this is a feedback control system (Fig. 8). Insuch a system, a desired output is sent to a comparator, which compares the present state of the

system with the desired output. If there is a mismatch between the present and desired outputs,

an error signal is sent to the effectormachinery that instructs it to bring the actual output closer to

the desired output. In order to detect the present state of the system, a sensormust be present tomeasure the present state of the system. The flow of information, from the comparator to the

effector, to the sensor, and back to the comparator, is called a closed loop.

A common example of a feedback control system is the thermostat in your home. The

thermostat is set to a desired temperature (e.g., 72), and a thermometer measures the currenttemperature in the room. If the comparator detects that the room is cooler than the desired

temperature, it sends an error signal that turns on the furnace. If the comparator detects that the

room is warmer than the desired setting, its sends an error signal that turns on the air conditioner.

EFFECTOR OUTPUTDESIRED OUTPUT +-

SENSORFeedback signal

Errorsignal

COMPARATOR

Fig. 8. A closed loop system with feedback control


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Feedback control systems can produce very accurate outputs; however, in general theyare slow. In order to change the output, the effector must wait until information is transmitted

from the sensor to the comparator and then to the effector. At this point, another comparison is

made, and the process continues. Consider further the thermostat example. If the temperaturereads 5 cooler than desired, the thermostat can instruct the furnace to turn on at a moderate heat.

It reads the new room temperature, and, if it is still too cool, it instructs the furnace to delivermore heat, and so on. Although this will eventually produce an accurate room temperature at thedesired point, it takes a number of cycles to reach that point. One possible solution for quicker

results would be to turn an enormous furnace on full-blast, such that is heats the room very

quickly. This solution, however, can generate another problem. It will tend to cause the system

to oscillate if the feedback pathways are slow. For example, assume that the furnace can heat theroom at the rate of 5 per second, but that it takes 2 seconds for the thermometer to adjust to the

new temperature, and for the new error signal to turn the furnace off. In those 2 seconds, the

furnace has heated the room up 10, and now it is too warm. So the error signal turns on the airconditioner, and it cools the room at 5/sec. Of course, it also takes 2 sec to receive the

feedback, and by the time it is told to shut off, it has cooled the room by 10. You can see what

happens: the system will be sent into an endless oscillation of being 5 too hot and 5 too cold.In order for a feedback system to work well, the transmission time of sensory information

through the comparator to the effector must be rapid compared to the time of the action.

Thus, the advantages of a feedback control system are:(1)It can produce very accurate output.(2)It is a very efficientmechanism in that all it requires of the operator is to set the desired

output level, and the system automatically adjusts itself to maintain that level. Theoperator does not need to manually turn the effectors on or off to constantly adjust the

movement.

The disadvantagesare

(1)It can be a slow system, often requiring many iterative cycles to produce the final desiredoutput.

(2)It is prone to oscillations.

As we shall see, many simple reflexes can be understood as feedback control systems, but such

systems are often too slow to control the accurate execution of many voluntary movements.

Open Loop System with Feedforward Control. A second manner in which sensoryinformation can be used to guide movements is by incorporating that information in advance of

the movement, during the planning and programming stages of motor execution. Such a system

is a feedforward control system (Fig. 9). In this type of system, when a desired output is sent tothe controller, the controller takes readings from sensors about the state of the environment and

about the current state of the effector itself. It then uses this information to program the best set

of instructions to accomplish the desired output. Importantly, in a pure feedforward system,once the commands to the effector are sent, there is no feedback pathway to alter the effector

during the execution of the movement. This is why it is termed an open loop system. Note

that a feedforward system differs from the open loop system with no sensory control, as thefeedforward system uses sensory information to plan the movement.


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The major advantage of the feedforward control system over the feedback system is

speed of execution. Whereas the feedback system can be slow and prone to oscillations, the

feedforward system (when working well) can produce the precise set of commands for theeffector without needing to constantly check the output and make corrections during the

movement itself. The main disadvantage, however, is that the feedforward controller requires aperiod oflearning before it can function properly. In most biological systems, the environmentand conditions under which actions are made are constantly changing, and the feedforward

controller must be able to adapt its output commands to account for this variability; it is hard

(perhaps impossible) to pre-program all of the possible sensory conditions that the controller

may encounter during the life of the organism.

Feed-forward

control signal

DESIRED

OUTPUTSENSOR

FEED-FORWARD

CONTROLLER

EFFECTOR

ADVANCE

INFORMATION

OUTPUT

Fig. 9. An open loop system with feedforward control uses sensory information in advance to output an appropriate

control signal to the effector.

Let us extend the thermostat example to see how a temperature controller operating as a

feedforward system would work to raise the temperature of a room from 70 to 75. The

controller would use diverse sensory information about the environment before sending itscommand to the furnace. For example, it would read the current temperature, the current

humidity level, the size of the room, the number of people in the room, and so forth. Based on

this information, it would direct the furnace to turn on for a pre-set period of time, and thats it.There would be no need to continually compare the current temperature with the desired setting,

as the system has predetermined how long the furnace needs to be working in order to achieve

the desired temperature. How did the controller obtain this information? A feedforward

controller requires a large amount of experience in order to learn the appropriate actions neededfor each set of environmental conditions. If on one trial it turns the furnace off too soon and the

room does not reach the desired temperature, it adjusts its programming such that the next time itencounters the same environmental conditions, it turns the furnace on for a longer period of time.

Through many such instances of trial and error learning, the feedforward system creates a look-

up table that tells it how long the furnace needs to be active under the current conditions. Thekey distinction between a feedback and feedforward system is that the feedback system uses

sensory information to generate an error signal during the control of a movement, whereas a

feedforward system uses sensory information in advance ofa movement. Any error signal about


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the final output is used by the feedforward system only to change its programming of futuremovements.

Thus, the advantages of a feedforward control system are(1)It is very accurate

(2)It is very fast(3)It does not require constant monitoring of the output during the execution of themovement

The disadvantages are

(1)It requires a period of learning before it can perform accurately

Motor deficits from sensory pathology. There are specific motor deficits seen withparticular sensory pathologies. The importance of feedback and feedforward control is evident

in the effects of loss of sensory input. This occurs in large fiber sensory neuropathy. A patient

with large fiber sensory neuropathy cannot sense their position nor detect motion of joints, sinceinput from muscle spindles and Golgi tendon organs is not present. Tactile information is also

impaired. Manual dexterity is devastated, since estimates of contact with objects cannot be made

precisely. However, pain and temperature sensation is preserved. These deficits are quite severe:

limb position can be maintained only if the patient can see them. In this case, patients must learnvisually guided, feedback and feedforward control strategies to compensate for the loss of

proprioceptive feedback and feedforward control signals. In severe cases, patients will collapse

the moment the lights are turned off, as they lose the visual feedback necessary to maintainposture and are unable to make coordinated movements at all.

As we will encounter repeatedly, feedback and feedforward control are distributed among

the hierarchical levels of motor control. Many movements are the result of combinations of both

feedback and feedforward control.


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MOTOR UNITS AND MUSCLE RECEPTORS

The Spinal Cord: The First Hierarchical Level

The spinal cord is the first level of the motor hierarchy. It is the site where motorneurons are located. It is also the site of many interneurons and complex neural circuits that

perform the nuts and bolts processing of motor control. These circuits execute the low-level

commands that generate the proper forces on individual muscles and muscle groups to enable

adaptive movements. Because this low level of the hierarchy takes care of these basic functions,higher levels (such as the motor cortex) can process information related to the planning of

movements, the construction of adaptive sequences of movements, and the coordination of

whole-body movements, without having to encode the precise details of each muscle contraction.

Motor Neurons

Alpha motor neurons (also called lower motor neurons) innervate skeletal muscle andcause the muscle contractions that generate movement. Motor neurons release the

neurotransmitter acetylcholine at a synapse called the neuromuscular junction. When the

acetylcholine binds to acetylcholine receptors on the muscle fiber, an action potential ispropagated along the muscle fiber in both directions. The action potential triggers the

contraction of the muscle. If the ends of the muscle are fixed, keeping the muscle at the same

length, then the contraction results on an increased force on the supports (isometric contraction).If the muscle shortens against no resistance, the contraction results in constant force (isotonic

contraction). The motor neurons that control limb and body movements are located in the

anterior horn of the spinal cord, and the motor neurons that control head and facial movements

are located in the motor nuclei of the brainstem. Even though the motor system is composed ofmany different types of neurons scattered throughout the CNS, the motor neuron is the only way

in which the motor system can communicate with the muscles. Thus, all movements ultimately

depend on the activity of lower motor neurons. The famous physiologist Sir Charles Sherringtonreferred to these motor neurons as the final common pathway in motor processing.

Motor neurons are not merely the conduits of motor commands generated from higher

levels of the hierarchy. They are themselves components of complex circuits that performsophisticated information processing. As shown in Figure 1, motor neurons have highly

branched, elaborate dendritic trees, enabling them to integrate the inputs from large numbers ofother neurons and to calculate proper outputs.

Figure 1. Spinal cord with motor neuron in anterior horn


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Two terms are used to describe the anatomical relationship between motor neurons and

muscles: the motor neuron pool and the motor unit.

(1)Motor neurons are clustered in columnar, spinal nuclei called motor neuron pools (ormotor nuclei). All of the motor neurons in a motor neuron pool innervate a single muscle(Figure 2), and all motor neurons that innervate a particular muscle are contained in thesame motor neuron pool. Thus, there is a one-to-one relationship between a muscle and a

motor neuron pool.

(2)Each individual muscle fiber in a muscle is innervated by one, and only one, motorneuron. A single motor neuron, however, can innervate many muscle fibers. The

combination of an individual motor neuron and all of the muscle fibers that it innervates

is called a motor unit. The number of fibers innervated by a motor unit is called its

innervation ratio.

If a muscle is required for fine control or for delicate movements (e.g., movement of the

fingers or hands), its motor units will tend to have a small innervation ratio. That is, each motorneuron will innervate a small number of muscle fibers (10-100), enabling many nuances of

movement of the entire muscle. If a muscle is required only for coarse movements (e.g., a thigh

muscle), its motor units will tend to have a high innervation ratio (i.e., each motor neuron

innervating 1000 or more muscle fibers), as there is no necessity for individual muscle fibers toundergo highly coordinated, differential contractions to produce a fine movement.

Control of Muscle Force

A motor neuron controls the amount of force that is exerted by muscle fibers. There aretwo principles that govern the relationship between motor neuron activity and muscle force: therate code and the size principle.

(1)Rate Code. Motor neurons use a rate code to signal the amount of force to be exerted by amuscle. An increase in the rate of action potentials fired by the motor neuron causes an

increase in the amount of force that the motor unit generates. This code is illustrated inFigure 3. When the motor neuron fires a single action potential, the muscle twitches slightly,

and then relaxes back to its resting state. If the motor neuron fires after the muscle has

Figure 2. Motor

unit and motor

neuron pool


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returned to baseline, then the magnitude of the next muscle twitch will be the same as thefirst twitch. However, if the rate of firing of the motor neuron increases, such that a second

action potential occurs before the muscle has relaxed back to baseline, then the second action

potential produces a greater amount of force than the first (i.e., the strength of the musclecontraction summates). With increasing firing rates, the summation grows stronger, up to a

limit. When the successive action potentials no longer produce a summation of musclecontraction (because the muscle is at its maximum state of contraction), the muscle is in astate called tetanus.

Figure 3. Rate code

(2)Size Principle. When a signal is sent to the motor neurons to execute a movement, motorneurons are not all recruited at the same time or at random. The motor neuronsize principle

states that, with increasing strength of input onto motor neurons, smaller motor neurons are

recruited and fire action potentials before larger motor neurons are recruited. Why does thisorderly recruitment occur? Recall from previous lectures the relationship between voltage,

current, and resistance (Ohms Law): V = IR. Because smaller motor neurons have a smaller

membrane surface area, they have fewer ion channels, and therefore a larger input resistance.Larger motor neurons have more membrane surface and correspondingly more ion channels;

therefore, they have a smaller input resistance. Because of Ohms Law, a small amount of

current will be sufficient to cause the membrane potential of a small motor neuron to reachfiring threshold, while the large motor neuron stays below threshold. As the amount of

current increases, the membrane potential of the larger motor neuron also increases, until it

also reaches firing threshold.

tetanus


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Figure 4. Size principle

Figure 4 demonstrates how the size principle governs the amount of force generated by amuscle. Because motor units are recruited in an orderly fashion, weak inputs onto motorneurons will cause only a few motor units to be active, resulting in a small force exerted by

the muscle. With stronger inputs, more motor neurons will be recruited, resulting in more

force applied to the muscle. Moreover, different types of muscle fibers are innervated bysmall and larger motor neurons. Small motor neurons innervate slow-twitch fibers;

intermediate-sized motor neurons innervate fast-twitch, fatigue-resistant fibers; and large

motor neurons innervatefast-twitch, fatigable muscle fibers. The slow-twitch fibers generateless force than the fast-twitch fibers, but they are able to maintain these levels of force for

long periods. These fibers are used for maintaining posture and making other low-force

movements. Fast-twitch, fatigue-resistant fibers are recruited when the input onto motor

neurons is large enough to recruit intermediate-sized motor neurons. These fibers generatemore force than slow-twitch fibers, but they are not able to maintain the force as long as theslow-twitch fibers. Finally, fast-twitch, fatigable fibers are recruited when the largest motor

neurons are activated. These fibers produce large amounts of force, but they fatigue very

quickly. They are used when the organism must generate a burst of large amounts of force,

such as in an escape mechanism. Most muscles contain both fast and slow-twitch fibers, butin different proportions. Thus, the white meat of a chicken, used to control the wings, is

composed primarily of fast-twitch fibers, whereas the dark meat, used to maintain balance

and posture, is composed primarily of slow-twitch fibers.

Figure 5 demonstrates how the rate code principle and the size principle interact to signal

muscle force. In this classic experiment by Monster and Chan (1977), the firing rate ofindividual motor neurons was measured as a function of the amount of force being generated by

a muscle. Each line on the graph corresponds to the firing rate of an individual motor neuron.

With small amounts of force, only a small number of motor neurons fire; these are the small

motor neurons that are recruited first. As the muscle generates increasing amounts of force,more and more motor neurons fire; these additional neurons are the larger motor neurons. This

is the size principle. Notice that as each individual motor neuron fires more rapidly, it produces

a greater force on the muscle. This is the rate code principle.


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Muscle Receptors and Proprioception

As discussed in the previous lecture, the motor system requires sensory input in order to

function properly. In addition to sensory information about the external environment, the motor

system also requires sensory information about the current state of the muscles and limbsthemselves. Proprioception is the sense of the bodys position in space based on specializedreceptors that reside in the muscles and tendons. The muscle spindle signals the length of a

muscle and changes in the length of a muscle. The Golgi tendon organ signals the amount of

force being applied to a muscle.

Muscle Spindles

Muscle spindles are collections of 6-8 specialized muscle fibers that are located within

the muscle mass itself (Figure 6). These fibers do not contribute significantly to the force

generated by the muscle. Rather, they are specialized receptors that signal (a) the length and (b)

the rate of change of length (velocity) of the muscle. Because of the fusiform shape of themuscle spindle, these fibers are referred to as intrafusal fibers. The large majority of muscle

fibers that actually contract and allow the muscle to do work are termed extrafusal fibers. Each

muscle contains many muscle spindles; muscles that are necessary for fine movements containmore spindles than muscles that are used for posture or coarse movements.

Figure 5. Interaction between

rate code and size principle in

determining muscle force.

Data from Monster AW &

Chan H (1977)Journal of

Neurophysiology 40:1432-

1443.

Figure 6. Muscle spindle and Golgi tendon

organ

Intrafusal fibers

Extrafusal fibers


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Types of muscle spindle fibers. There are 3 types of muscle spindle fibers,characterized by their shape and the type of information they convey (Figure 7).

(1)Nuclear Chain fibers. These fibers are so-named because their nuclei are aligned ina single row (chain) in the center of the fiber. They signal information about the

static length of the muscle.(2)Static Nuclear Bag fibers. These fibers are so-named because their nuclei arecollected in a bundle in the middle of the fiber. Like the nuclear chain fiber, these

fibers signal information about the static length of a muscle.

(3)Dynamic Nuclear Bag fibers. These fibers are anatomically similar to the staticnuclear bag fibers, but they signal primarily information about the rate of change(velocity) of muscle length.

A typical muscle spindle is composed of 1 dynamic nuclear bag fiber, 1 static nuclear bag fiber,

and ~5 nuclear chain fibers.

Sensory innervation of muscle spindles. Because the muscle spindle is located in

parallel with the extrafusal fibers, it will stretch along with the muscle. The muscle spindle

signals muscle length and velocity to the CNS through two types of specialized sensory fibersthat innervate the intrafusal fibers. These sensory fibers have stretch receptors that open and

close as a function of the length of the intrafusal fiber.

(1)Group Ia afferents (also called primary afferents) wrap around the central portion ofall 3 types of intrafusal fibers; these specialized endings are called annulospiralendings. Because they innervate all 3 types of intrafusal fibers, Group Ia afferentsprovide information about both length and velocity.

(2)Group II afferents (secondary afferents) innervate the ends of the nuclear chainfibers and the static nuclear bag fibers at specialized junctions termed flower sprayendings. Because they do not innervate the dynamic nuclear bag fibers, Group IIafferents signal information about muscle length only.

Figure 7. Muscle spindle detail


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Because of their patterns of innervation onto the three types of intrafusal fibers, Group Iaand Group II afferents respond differently to different types of muscle movements. Figure 8

shows the responses of each type of afferent to a linear stretch of the muscle. Initially, both

Group Ia and Group II fibers fire at a certain rate, encoding the current length of the muscle.During the stretch, the two types differ in their responses. The Group Ia afferent fires at a very

high rate during the stretch, encoding the velocity of the muscle length; at the end of the stretch,its firing decreases, as the muscle is no longer changing length. Note, however, that its firingrate is still higher than it was before the stretch, as it is now encoding the new length of the

muscle. Compare the response of the Group Ia afferent to the Group II afferent. The Group II

afferent increases its firing rate steadily as the muscle is stretched. Its firing rate does not depend

on the rate of change of the muscle; rather, its firing rate depends only on the immediate lengthof the muscle.

Figure 8. Responses of muscle spindles

Gamma motor neurons. Although intrafusal fibers do not contribute significantly tomuscle contraction, they do have contractile elements at their ends that are innervated by motor

neurons. Motor neurons are divided into two groups. Alpha motor neurons innervate extrafusal

fibers, the contracting fibers that supply the muscle with its power. Gamma motor neuronsinnervate intrafusal fibers, which contract only slightly. The function of intrafusal fiber

contraction is not to provide force to the muscle; rather, gamma activation of the intrafusal fiber

is necessary to keep the muscle spindle taut, and therefore sensitive to stretch, over a wide rangeof muscle lengths. This concept is illustrated in Figure 9. If a resting muscle is stretched, the

muscle spindle becomes stretched in parallel, sending signals through the primary and secondary

afferents. A subsequent contraction of the muscle, however, removes the pull on the spindle, andit becomes slack, causing the spindle afferents to cease firing. If the muscle were to be stretched

again, the muscle spindle would not be able to signal this stretch. Thus, the spindle is rendered

temporarily insensitive to stretch after the muscle has contracted. Activation of gamma motor

neurons prevents this temporary insensitivity by causing a weak contraction of the intrafusal

fibers, in parallel with the contraction of the muscle. This contraction keeps the spindle taut atall times and maintains its sensitivity to changes in the length of the muscle. Thus, when the

CNS instructs a muscle to contract, it not only sends the appropriate signals to the alpha motorneurons, it also instructs gamma motor neurons to contract the intrafusal fibers appropriately;

this coordinated process is referred to as alpha-gamma coactivation.


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Golgi Tendon Organ

The Golgi tendon organ is a specialized receptor that is located between the muscle andthe tendon (Figure 6). Unlike the muscle spindle, which is located in parallel with extrafusal

fibers, the Golgi tendon organ is located in series with the muscle and signals information about

the load or force being applied to the muscle.

A Golgi tendon organ is made up of a capsule containing numerous collagen fibers

(Figure 10). The organ is innervated by primary afferents called Group Ib fibers, which havespecialized endings that weave in between the collagen fibers. When force is applied to a

muscle, the Golgi tendon organ is stretched, causing the collagen fibers to squeeze and distort themembranes of the primary afferent sensory endings. As a result, the afferent is depolarized, and

it fires action potentials to signal the amount of force.

Figure 10. Golgi tendon organ detail

Group Ib afferent

Figure 9. Gamma activation of intrafusal

fibers. (A) Muscle is at a certain length,

encoded by firing of Ia afferent. (B) When

muscle is stretched, muscle spindle stretches

and Ia afferent fires more strongly. (C) When

muscle is contracted again, muscle spindlebecome slack, causing Ia afferent to fall silent.

The muscle spindle is rendered insensitive to

further stretches of muscle. (D) To restore

sensitivity, firing of gamma motor neurons

causes spindle to contract, thereby becoming

taut and able to signal.


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In summary,

(1) Muscle spindles signal information about the length and velocity of a muscle

(2) Golgi tendon organs signal information about the loadorforce applied to a muscle

Functions of Muscle Spindles and Golgi Tendon Organs: An Introduction to SpinalReflexes

As noted in the previous lecture, a sense of body position is necessary for adaptive motor

control. In order to move a limb toward a particular location, it is imperative to know the initial

starting position of the limb, as well as any force applied to the limb. Muscle spindles and Golgitendon organs provide this type of information. In addition, these receptors are components of

certain spinal reflexes that are important for both clinical diagnoses as well as for a basic

understanding of the principles of motor control.

Myotatic reflex

The myotatic reflex is illustrated in Figure 11. A waiter is holding an empty tray, when

unexpectedly a pitcher of water is placed on the tray. Because the waiters muscles were not

prepared to support the increased weight, the tray should fall. However, a spinal reflex is

automatically initiated to keep the tray relatively stable. When the heavy pitcher is placed on thetray, the increased weight stretches the biceps muscle, which results in the activation of the

muscle spindles Ia afferents. The Ia afferents have their cell bodies in the dorsal root ganglia of

the spinal cord, send projections into the spinal cord, and make synapses directly on alpha motorneurons that innervate the same (homonymous) muscle. Thus, activation of the Ia afferent

causes a monosynaptic activation of the alpha motor neuron that causes the muscle to contract.As a result, the stretch of the muscle is quickly counteracted, and the waiter is able to maintain

the tray at the same position.

Figure 11. Myotatic reflex

The myotatic reflex is an example of a feedback control system (discussed in the previous

lecture). A comparator (the spindle) compares the desired output (hold the limb steady at a

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particular position) with the current state of the system. Initially, when the tray is steady, there isno difference between the desired output and the current state. When the pitcher is placed on the

tray, however, the muscle spindle is stretched, and this causes the Ia afferent to send an error

signal that the muscle is stretched more than the desired output. The alpha motor neuron thencauses the effector (the muscle) to contract, thereby realigning the current state of the system

with the desired output.

A major role of the myotatic reflex is the maintenance of posture. Recall that feedback

control mechanisms are slow, and are typically not useful for rapid, voluntary movements. For

maintaining static posture, however, feedback mechanisms are very efficient and accurate. If

one is standing upright and starts to sway to the left, muscles in the legs and torso are stretched,activating the myotatic reflex to counteract the sway. In this way, the higher levels of the motor

system are able to send a simple command (maintain current posture) and then be uninvolved

in its implementation. The lower levels of the hierarchy implement the command with suchmechanisms as the myotatic reflex, freeing the higher levels to perform other tasks such as

planning the next sequence of movements.

The myotatic reflex is an important clinical reflex. It is the same circuit that produces the

knee-jerk, or stretch, reflex. When the physician taps the patellar tendon with a hammer, this

action causes the knee extensor muscle to stretch momentarily. This stretch activates the

myotatic reflex, causing an extension of the lower leg. (Because the physician taps the tendon,this reflex is also referred to as the deep tendon reflex. Do not be confused, however, between

this terminology and the Golgi tendon organ. The myotatic reflex is initiated by the muscle

spindle, not the Golgi tendon organ.) As we will learn in the next lecture, spinal reflexes can bemodulated by higher levels of the hierarchy, and thus a hyperactive or hypoactive stretch reflex

is an important clinical sign to localize neurological damage.

Autogenic inhibition

The Golgi tendon organ is involved in a spinal reflex known as the autogenic inhibition

reflex (Figure 12). When tension is applied to a muscle, the Group Ib fibers that innervate the

Golgi tendon organ are activated. These afferents have their cell bodies in the dorsal rootganglia, and they project into the spinal cord and synapse onto an interneuron called the Ib

inhibitory interneuron. This interneuron makes an inhibitory synapse onto the alpha motor

neuron that innervates the same muscle that caused the Ib afferent to fire. As a result of this

reflex, activation of the Ib afferent causes the muscle to cease contraction, as the alpha motorneuron becomes inhibited. Because this reflex contains an interneuron between the sensory

afferent and the motor neuron, it is an example of a disynaptic reflex.


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Figure 12. Autogenic inhibition

For many years, it was thought that the function of the autogenic inhibition circuit was to

protect the muscle from excessive amounts of force that might damage it. A classic example is

that of the weightlifter straining to raise a heavy load, when suddenly the autogenic inhibition

reflex is activated and the muscle loses power, causing the weight to fall to the ground. Thisfunction was ascribed to the reflex because early work suggested that the Golgi tendon organ

was only activated when large amounts of force were applied to it. More recent evidence

indicates, however, that the Golgi tendon organ is sensitive to much lower levels of force thanpreviously believed. This finding suggests that the autogenic inhibition reflex may be more

extensively involved in motor control under normal conditions. One possibility is that this reflex

helps to spread the amount of work evenly across the entire muscle, so that all motor units are

working efficiently. That is, if some muscle fibers are bearing more of the load than others, theirGolgi tendon organs will be more active, which will tend to inhibit the contraction of those

fibers. As a result, other muscle fibers that are less active will have to contract more to pick up

the slack, thereby sharing the work load more efficiently. This hypothesized function is anotherexample of a feedback control system.

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SPINAL RELEXES AND DESCENDING MOTOR PATHWAYS

Spinal reflexes

The end of the last lecture introduced two simple spinal reflexes that are initiated by

proprioceptors: the myotatic (stretch) reflex, which is initiated by the muscle spindle, and theautogenic inhibition reflex, which is initiated by the Golgi tendon organ. In each case, activationof a muscle receptor causes a change in the alpha motor neurons that innervate the same muscle.

The production of adaptive, coordinated behaviors requires further sophistication in these simple

reflexes. For example, stretching the muscle spindle not only leads to the contraction of the

homonymous muscle by the myotatic reflex, but also leads to the contraction of synergistmuscles by collateral pathways. The following are further examples of more sophisticated reflex

pathways.

Reciprocal inhibition in the stretch reflex. Joints are controlled by two opposing sets of

muscles, extensors and flexors, which must work in synchrony. Thus, when a muscle spindle is

stretched and activates the stretch reflex, the opposing muscle group must be inhibited to preventit from working against the resulting contraction of the homonymous muscle (Fig. 1). This

inhibition is accomplished by an inhibitory interneuron in the spinal cord. The Ia afferent of the

muscle spindle bifurcates in the spinal cord. One branch innervates the alpha motor neuron that

causes the homonymous muscle to contract, producing the behavioral reflex. The other branchinnervates the Ia inhibitory interneuron, which in turn innervates the alpha motor neuron that

synapses onto the opposing muscle. Because the interneuron is inhibitory, it prevents the

opposing alpha motor neuron from firing, thereby reducing the contraction of the opposingmuscle. Without this reciprocal inhibition, both groups of muscles might contract together and

work against each other.

Figure 1: Reciprocal inhibition in stretch reflex

Reciprocal excitation in the autogenic inhibition reflex. Just as in the stretch reflex,

the autogenic inhibition reflex (initiated by the Golgi tendon organ) must coordinate the activity

of the extensor and flexor muscle groups (Fig. 2). The Ib afferent fiber bifurcates in the spinalcord. One branch innervates the Ib inhibitory interneuron, as described in the last lecture. The

other branch innervates an excitatory interneuron that, in turn, innervates the alpha motor neuron

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that controls the antagonist muscle. Thus, when the homonymous muscle is inhibited fromcontracting, the antagonist muscle is caused to contract, allowing the opposing muscle groups to

work in synchrony.

Figure 2: Reciprocal excitation in the autogenic inhibition reflex

Flexor reflex. Spinal reflexes can be initiated by nonproprioceptive receptors as well as

by proprioceptors. An important reflex initiated by cutaneous receptors and pain receptors is theflexor reflex. We have all experienced this reflex after accidentally touching a hot stove or a

sharp object, as we withdraw our hand even before we consciously experience the sensation of

pain. This quick reflex removes the limb from the damaging stimulus more quickly than if the

pain signal had to travel up to the brain, be brought to conscious awareness, and then trigger adecision to withdraw the limb. The reflex circuit is illustrated in Figure 3. A sharp object

touching the foot causes the activation of Group III afferents of pain receptors. These afferents

enter the spinal cord and then travel up the cord. A branch of the afferent innervates anexcitatory interneuron in the lumbar region of the spinal cord, which then excites an alpha motor

neuron that causes contraction of the thigh flexor muscle. The Group III afferent also continuesupward to the L2 vertebra, where another branch innervates an excitatory interneuron at this

level. This interneuron excites the alpha motor neurons that excite the hip flexor muscle,

allowing the coordinated activity of two muscle groups to withdraw the whole leg away from thepainful stimulus. Thus, spinal reflexes work not only at a single joint; they can also coordinate

the activity of multiple joints simultaneously.

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Figure 3: Flexor reflex

Reciprocal inhibition in the flexor reflex. When the knee joints and the hip joints are

flexed, the antagonist extensor muscles must be inhibited (just as in the stretch reflex). This isaccomplished by the Group III afferents innervating inhibitory interneurons that in turn innervatethe alpha motor neurons controlling the antagonist muscle.

Crossed extension reflex. Although the flexor reflex as described works well tosynchronize the activity of multiple muscle groups to allow the coordinated movement of the

entire limb, further circuitry is needed to make the reflex adaptive. Because the weight of the

body is supported by both legs, the flexor reflex must coordinate the activity not only of the leg

being withdrawn but also of the opposite leg (Fig. 4). Imagine stepping on a tack, and having theflexor reflex withdraw your right leg immediately. The left leg must simultaneously extend in

order to support the body weight that would have been supported by the left leg. Without this

coordination of the two legs, the shift in body mass would cause a loss of balance. Thus, theflexor reflex incorporates a crossed extension reflex. A branch of the Group III afferent

innervates an excitatory interneuron that sends its axon across the midline into the contralateral

spinal cord. There it excites the alpha motor neurons that innervate the extensor muscles of theopposite leg, allowing balance and body posture to be maintained.


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Figure 4: Crossed extension reflex

Recurrent inhibition of motor neurons (Renshaw cells).

Axons of alpha motorneurons bifurcate in the spinal cord and innervate a special inhibitory interneuron called the

Renshaw cell (Fig. 5). This interneuron innervates and inhibits the very same motor neuron that

caused it to fire. Thus, a motor neuron regulates its own activity by inhibiting itself when it fires.This negative feedback loop is thought to stabilize the firing rate of motor neurons.

Figure 5: Renshaw cell

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Descending Motor Pathways

The spinal reflex circuits described above demonstrate that quite sophisticated and

precise neural processing occurs at the lowest level of the motor hierarchy. These automaticreflexes can be modulated, however, by higher levels of the hierarchy. For example, when

touching an iron to see if it is still hot, your flexor reflex may be even more sensitive thannormal. As a result, you pull your hand away repeatedly before even touching the iron,anticipating that it may be hot. Conversely, if you are removing a hot dish from the oven and the

heat starts to go through the oven mitt, you will suppress the flexor response so that you do not

drop your dinner all over the floor as you rush to put it down on a counter top. These

modulations (both facilitatory and inhibitory) of the spinal reflexes arise from the descendingpathways from the brainstem and cortex. Additionally, voluntary movement, as well as

vestibular-, visual-, and auditory-driven reflex actions, are controlled by the descending

pathways.

Descending motor pathways arise from multiple regions of the brain and send axons

down the spinal cord that innervate alpha motor neurons, gamma motor neurons, andinterneurons. The motor neurons are topographically organized in the anterior horn of the spinal

cord according to two rules: the flexor-extensor rule and the proximal-distal rule.

Flexor-extensor rule: motor neurons that innervate flexor muscles are located posteriorly tomotor neurons that innervate extensor muscles.

Proximal-distal rule: motor neurons that innervate distal muscles (e.g., hand muscles) arelocated lateral to motor neurons that innervate proximal muscles (e.g., trunk muscles).

Figure 6: Flexor-extensor/proximal-distal rules

Descending motor pathways are organized into two major groups:

(1) Lateral pathways control both proximal and distal muscles and are responsible for mostvoluntary movements of arms and legs. They include the

(a) lateral corticospinal tract

(b) rubrospinal tract


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(2) Medial pathways control axial muscles and are responsible for posture, balance, and coarse

control of axial and proximal muscles. They include the

(a) vestibulospinal tracts (both lateral and medial)(b) reticulospinal tracts (both pontine and medullary)

(c) tectospinal tract(d) anterior corticospinal tract

Corticospinal tracts. The corticospinal tract originates in the motor cortex (Fig. 7). The

axons of motor projection neurons collect in the internal capsule, and then course through the

crus cerebri (cerebral peduncle) in the midbrain. At the level of the medulla, these axons formthe medullary pyramids on the ventral surface of the brainstem (hence, this tract is also called the

pyramidal tract). At the level of the caudal medulla, the corticospinal tract splits into two tracts.

Approximately 90% of the axons cross over to the contralateral side at the pyramidaldecussation, forming the lateral corticospinal tract. These axons continue to course through the

lateral funiculus of the spinal cord, before synapsing either directly onto alpha motor neurons or

onto interneurons in the ventral horn. The remaining 10% of the axons that do not cross at thecaudal medulla constitute the anterior corticospinal tract, as they continue down the spinal cord

in the anterior funiculus. When they reach the spinal segment at which they terminate, they cross

over to the contralateral side through the anterior white commissure and innervate alpha motor

neurons or interneurons in the anterior horn. Thus, both the lateral and anterior corticospinaltracts are crossed pathways; they cross the midline at different locations, however.

Function. The corticospinal tract(along with the corticobulbar tract) is the

primary pathway that carries the motorcommands that underlie voluntary

movement. The lateral corticospinal tract is

responsible for the control of the distalmusculature and the anterior corticospinal

tract is responsible for the control of the

proximal musculature. A particularlyimportant function of the lateral

corticospinal tract is the fine control of the

digits of the hand. The corticospinal tract is

the only descending pathway in which someaxons make synaptic contacts directly onto

alpha motor neurons. This direct cortical

innervation presumably is necessary toallow the powerful processing networks of

the cortex to control the activity of the

spinal circuits that direct the exquisitemovements of the fingers and hands. The

percentage of axons in the corticospinal tract

that innervate alpha motor neurons directlyis greater in humans and nonhuman

Figure 7: Corticospinal tracts


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primates than in other mammals, presumably reflecting the increased manual dexterity ofprimates. Damage to the corticospinal tract results in a permanent loss of the fine control of the

extremities. Although parallel descending pathways can often recover the function of more

coarse movements, these pathways are not capable of generating fine, skilled movements. Inaddition to the fine control of distal muscles, the corticospinal tract also plays a role in the

voluntary control of axial muscles.

Rubrospinal tract. The rubrospinal tract

originates in the red nucleus of the midbrain (Fig.

8). The axons immediately cross to the

contralateral side of the brain, and they coursethrough the brainstem and the lateral funiculus of

the spinal cord. The axons innervate spinal

neurons at all levels of the spinal cord.

Function. The rubrospinal tract is an alternative

by which voluntary motor commands can be sentto the spinal cord. Although it is a major pathway

in many animals, it is relatively minor in humans.

Activation of this tract causes excitation of flexor

muscles and inhibition of extensor muscles. Therubrospinal tract is thought to play a role in

movement velocity, as rubrospinal lesions cause a

temporary slowness in movement. In addition,because the red nucleus receives most of its input

from the cerebellum, the rubrospinal tract probablyplays a role in transmitting learned motor

commands from the cerebellum to the

musculature. The red nucleus also receives someinput from the motor cortex, and it is therefore

probably an important pathway for the recovery of

some voluntary motor function after damage to thecorticospinal tract.

Vestibulospinal tracts. The two vestibulospinal tracts originatein 2 of the 4 vestibularnuclei (Fig. 9). The lateral vestibulospinal tract originates in the lateral vestibular nucleus. It

courses through the brainstem and through the anterior funiculus of the spinal cord on the

ipsilateral side, before exiting ipsilaterally at all levels of the spinal cord. The medialvestibulospinal tract originates in the medial vestibular nucleus, splits immediately and courses

bilaterally through the brainstem via the medial longitudinal fasciculus and through the anterior

funiculus of the spinal cord, before exiting at or above the T6 vertebra.

Function. The vestibulospinal tracts mediate postural adjustments and head movements.

They also help the body to maintain balance. Small movements of the body are detected by thevestibular sensory neurons, and motor commands to counteract these movements are sent

Figure 8: Rubrospinal tract


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through the vestibulospinal tracts to appropriatemuscle groups throughout the body. The lateral

vestibulospinal tract excites antigravity muscles

in order to exert control over postural changesnecessary to compensate for tilts and

movements of the body. The medialvestibulospinal tract innervates neck muscles inorder to stabilize head position as one moves

around the world. It is also important for the

coordination of head and eye movements.

Reticulospinal tracts. The two reticulospinal tracts

originate in the brainstem reticular formation, a large,

diffusely organized collection of neurons in the pons andmedulla (Fig. 10). The pontine reticulospinal tract

originates in the pontine reticular formation, courses

ipsilaterally through the medial longitudinal fasciculus andthrough the anterior funiculus of the spinal cord, and exits

ipsilaterally at all spinal levels. The medullary

reticulospinal tract originates in the medullary reticular

formation, courses mainly ipsilaterally (although somefibers cross the midline) through the anterior funiculus of

the spinal cord, and exits at all spinal levels.

Function. The reticulospinal tracts are a major

alternative to the corticospinal tract, by which cortical

neurons can control motor function by their inputs ontoreticular neurons. These tracts regulate the sensitivity of

flexor responses to ensure that only noxious stimuli elicit the responses. Damage to thereticulospinal tract can thus cause harmless stimuli, such as gentle touches, to elicit a flexor

Figure 9: Vestibulospinal tracts

Figure 10: Reticulospinal tracts


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reflex. The reticular formation also contains circuitry for many complex actions, such asorienting, stretching, and maintaining a complex posture. Commands that initiate locomotor

circuits in the spinal cord are also thought to be transmitted through the medullary reticulospinal

tract. Thus, the reticulospinal tracts are involved in many aspects of motor control, including theintegration of sensory input to guide motor output.

Tectospinal tract. The tectospinal tract originates inthe deep layers of the superior colliculus and crosses the

midline immediately. It then courses through the pons and

medulla, just anterior to the medial longitudinal fasciculus. It

courses through the anterior funiculus of the spinal cord,where the majority of the fibers terminate in the upper cervical

levels.

Function. Little is known about the function of the

tectospinal tract, but because of the nature of the visual

response properties of neurons in the superior colliculus (theoptic tectum), it is presumably involved in the reflexive

turning of the head to orient to visual stimuli.

Figure 11: Tectospinal tract

Influences of descending pathways on spinal circuits

Voluntary movement. The most distinctive function of the descending motor pathwaysis the control of voluntary movement. These movements are initiated in the cerebral cortex, and

the motor commands are transmitted to the musculature through a variety of descending

pathways, including the corticospinal tract, the rubrospinal tract, and reticulospinal tracts. Howvoluntary movements are initiated and coordinated by the motor cortex is the subject of the next

lecture.

Reflex modulation. Another critical function of the descending motor pathways is to

modulate the reflex circuits in the spinal cord. The adaptiveness of spinal reflexes can change

depending on the behavioral context; sometimes the gain (strength) or even the sign (extensionvs. flexion) of a reflex must be changed in order to make the resulting movement adaptive. The

descending pathways are responsible for controlling these variables. For example, consider theflexor reflex under two conditions.


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(a) Imagine a situation in which you want to pick up a dish from the stove top, but youare uncertain whether it is hot or cold. You may attempt to lightly touch the surface, and this

will often lower the threshold of the flexor reflex, making you more likely to pull your hand

away even if the dish is not particularly hot. (You may even withdraw your hand numeroustimes before even touching the dish!) Descending pathways have lowered the threshold for

producing the reflex in this case, making it easier for a weaker nociceptive input to trigger thereflex; these pathways can also change the gain of the reflex, making the withdrawal responsegreater than usual.

(b) Imagine now picking up the dish in order to move it to the table. As you hold the dish,

more of its heat begins to transfer to your hand, and it starts to get quite hot. Rather thandropping the dish and spilling your dinner all over the floor, you rush to the table to put it down,

before withdrawing your hand and wishing you had used an oven mitt. In this case, the

descending pathways inhibited the flexor response.

Gamma bias. Recall from the previous lecture that there are two types of spinal motor

neurons. Alpha motor neurons innervate extrafusal muscle fibers, which provide the force for amuscle contraction. Gamma motor neurons innervate the ends of intrafusal fibers and help to

maintain the tautness of muscle spindles, such that they are sensitive to changes of muscle length

over a wide range. In order to work adaptively, the activity of alpha and gamma motor neurons

must be coordinated. Thus, whenever motor commands are sent by descending pathways toalpha motor neurons, the appropriate compensating commands are sent to gamma motor neurons.

This coordination of alpha-gamma motor commands is called alpha-gamma coactivation, and the

adjustment of spindle sensitivity by gamma activation is called gamma bias. Consider thefollowing two examples:

(a) When a command is given to a muscle to contract, the muscle spindles become slack,

thereby making them insensitive to further changes in muscle length. To compensate for this,

the gamma motor neurons that innervate these intrafusal muscle fibers are activated in concertwith the alpha motor neurons, allowing the intrafusal fibers to contract with the muscle. This

preserves the sensitivity of the muscle to unexpected stretches of the muscle.

(b) When a muscle contracts, the antagonist muscle is stretched during the movement.

An obvious problem arises when one considers the stretch reflex of the antagonist muscle. If

contraction of a muscle causes the activation of the stretch reflex of the antagonist muscle, the

antagonist muscle will contract to resist the movement of the limb. How is it possible to everflex a joint when the stretch reflex of the extensor muscle causes it to extend the joint instead?

Alpha-gamma coactivation solves this problem by relaxing the contraction of the intrafusal fibers

of the antagonist muscle, allowing the muscle to be stretched without triggering the stretch reflexduring a voluntary movement.


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CEREBELLUM

Overview: Functions of the cerebellum

The cerebellum (little brain) is a structure that is located at the back of the brain,underlying the occipital and temporal lobes of the cerebral cortex (Fig. 1). Although thecerebellum accounts for approximately 10% of the brains volume, it contains over 50% of the

total number of neurons in the brain. Historically, the cerebellum has been considered a motor

structure, because cerebellar damage leads to impairments in motor control and posture and

because the majority of the cerebellums outputs are to parts of the motor system. Motorcommands are not initiated in the cerebellum; rather, the cerebellum modifies the motor

commands of the descending pathways to make movements more adaptive and accurate. The

cerebellum is involved in the following functions:

Figure 1. Cerebellum

Maintenance of balance and posture. The cerebellum is important for making posturaladjustments in order to maintain balance. Through its input from vestibular receptors and

proprioceptors, it modulates commands to motor neurons to compensate for shifts in body

position or changes in load upon muscles. Patients with cerebellar damage suffer from balancedisorders, and they often develop stereotyped postural strategies to compensate for this problem

(e.g., a wide-based stance).

Coordination of voluntary movements. Most movements are composed of a number of

different muscle groups acting together in a temporally coordinated fashion. One major functionof the cerebellum is to coordinate the timing and force of these different muscle groups to

produce fluid limb or body movements.

Motor learning. The cerebellum is important for motor learning. The cerebellum plays a

major role in adapting and fine-tuning motor programs to make accurate movements through a

trial-and-error process (e.g., learning to hit a baseball).

Cognitive functions. Although the cerebellum is most understood in terms of its

contributions to motor control, recent studies have revealed that it is also involved in certain

cognitive functions, such as language. Thus, like the basal ganglia, the cerebellum is historically


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considered as part of the motor system, but its functions extend beyond motor control in waysthat are not well understood.

Cerebellar gross anatomy

The cerebellum consists of two major parts (Fig. 2A). The cerebellar deep nuclei (orcerebellar nuclei) are the sole output structures of the cerebellum. These nuclei are encased by ahighly convoluted sheet of tissue called the cerebellar cortex, which contains almost all of the

neurons in the cerebellum. A cross-section through the cerebellum reveals the intricate pattern

of folds and fissures that characterize the cerebellar cortex. Like the cerebral cortex, cerebellar

gyri are reproducible across individuals and have been identified and named. We will only beconcerned with some of the larger divisions of the cerebellar cortex.

Figure 2. (A) Cerebellar deep nuclei and cerebellar cortex in an idealized brain section. (B)External morphology of the cerebellum

Divisions of the cerebellum. Two major fissures running mediolaterally divide the

cerebellar cortex into 3 primary subdivisions (Fig. 2B, Fig. 3). The posterolateral fissureseparates the flocculonodular lobe from the corpus cerebelli, and the primary fissure separates

the corpus cerebelli into a posterior lobe and an anterior lobe. The cerebellum is also divided

sagittally into 3 zones that run from medial to lateral (Figure 3). The vermis (from the Latinword for worm) is located along the midsagittal plane of the cerebellum. Directly lateral to the

vermis is the intermediate zone. Finally, the lateral hemispheres are located lateral to the

intermediate zone (there are no clear morphological borders between the intermediate zone andthe lateral hemisphere that are visible from a gross specimen).

Cerebellar nuclei. All output from the cerebellum originates from the cerebellar deep

nuclei. Thus, a lesion to the cerebellar nuclei has the same effect as a complete lesion of theentire cerebellum. It is important to know the inputs, outputs, and anatomical relationships

between the different cerebellar nuclei and the subdivisions of the cerebellum (Fig. 4).


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Figure 3. Divisions of cerebellum

(1) The fastigial nucleus is the most medially located of the cerebellar nuclei. It receives

input from the vermis and from cerebellar afferents that carry vestibular, proximalsomatosensory, auditory, and visual information. It projects to the vestibular nuclei and the

reticular formation.

(2) The interposed nuclei comprise the emboliform nucleus and the globose nucleus.

They are situated lateral to the fastigial nucleus. They receive input from the intermediate zoneand from cerebellar afferents that carry spinal, proximal somatosensory, auditory, and visual

information. They project to the contralateral red nucleus (the origin of the rubrospinal tract).

(3) The dentate nucleus is the largest of the cerebellar nuclei, located lateral to the

interposed nuclei. It receives input from the lateral hemisphere and from cerebellar afferents thatcarry information from the cerebral cortex (via the pontine nuclei). It projects to the contralateral

red nucleus and the ventrolateral (VL) thalamic nucleus.

(4) The vestibular nuclei are located outside the cerebellum, in the medulla. Hence, they

are not strictly cerebellar nuclei, but they are considered to be functionally equivalent to the

cerebellar nuclei because their connectivity patterns are identical to the cerebellar nuclei. Thevestibular nuclei receive input from the flocculonodular lobe and from the vestibular labyrinth.

They project to various motor nuclei and originate the vestibulospinal tracts.

In addition to these inputs, all cerebellar nuclei and all regions of cerebellum get specialinputs from the inferior olive of the medulla (discussed below).


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It is convenient to remember that the anatomical locations of the cerebellar nucleicorrespond to the cerebellar cortex regions from which they receive input. Thus, the medially

located fastigial nucleus receives input from the medially located vermis; the slightly lateral

interposed nuclei receive input from the slightly lateral intermediate zone; and the most lateraldentate nucleus receives input from the lateral hemispheres.

Figure 4. Inputs/outputs of cerebellum


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Cerebellar peduncles. Three major bundles of fibers carry the input and output of thecerebellum.

(1) The inferior cerebellar peduncle (also called the restiform body) primarily containsafferent fibers from the medulla, as well as efferents to the vestibular nuclei.

(2) The middle cerebellar peduncle (also called the brachium pontis) primarily containsafferents from the pontine nuclei.

(3) The superior cerebellar peduncle (also called the brachium conjunctivum) primarily

contains efferent fibers from the cerebellar nuclei, as well as some afferents from thespinocerebellar tract.

Thus, the inputs to the cerebellum are conveyed primarily through the inferior and middlecerebellar peduncles whereas the outputs are conveyed primarily through the superior cerebellar

peduncle. The inputs arise from the ipsilateral side of the body, and the outputs also go to the

ipsilateral side of the body. Note that this is true even for the outputs to the contralateral rednucleus. Recall from the lecture on descending motor pathways that the rubrospinal tract

immediately crosses the midline after the fibers leave the red nucleus. Thus, cerebellar output to

the red nucleus affects the ipsilateral side of the body by a double-crossed pathway. Unlike the

cerebral cortex, the cerebellum receives input from, and controls output to, the ipsilateral side ofthe body, and damage to the cerebellum therefore results in deficits to the ipsilateral side of the

body.

Functional subdivisions of the cerebellum

The anatomical subdivisions described above correspond to three major functional

subdivisions of the cerebellum.

(1) The vestibulocerebellum comprises the flocculonodular lobe and its connections

with the lateral vestibular nuclei. Phylogenetically, the vestibulocerebellum is the oldest part of

the cerebellum. As its name implies, it is involved in vestibular reflexes (such as thevestibuloocular reflex; see below) and in postural maintenance.

(2) The spinocerebellum comprises the vermis and the intermediate zones of the

cerebellar cortex, as well as the fastigial and interposed nuclei. As its name implies, it receivesmajor inputs from the spinocerebellar tract. Its output projects to rubrospinal, vestibulospinal,

and reticulospinal tracts. It is involved in the integration of sensory input with motor commands

to produce adaptive motor coordination.

(3) The cerebrocerebellum is the largest functional subdivision of the human

cerebellum, comprising the lateral hemispheres and the dentate nuclei. Its name derives from itsextensive connections with the cerebral cortex, via the pontine nuclei (afferents) and the VL

thalamus (efferents). It is involved in the planning and timing of movements. In addition, the

cerebrocerebellum is involved in the recently discovered, yet poorly understood, cognitivefunctions of the cerebellum.


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Histology and connectivity of cerebellar cortex

The cerebellar cortex is divided into 3 layers (Fig. 5). The innermost layer, the granule

cell layer, is made of 5 x 1010

small, tightly packed granule cells. The middle layer, the Purkinjecell layer, is only 1-cell thick. The outer layer, the molecular layer, is made of the axons of

granule cells and the dendrites of Purkinje cells, as well as a few other cell types. The Purkinjecell layer forms the border between the granule and molecular layers.

Figure 5. Cerebellar circuitry. This basic pattern is repeated throughout all regions of the cerebellum.

Granule cells. Granule cells are very small, densely packed neurons that account for thehuge majority of neurons in the cerebellum. Indeed, cerebellar granule cells account for more

than half of the neurons in the entire brain. These cells receive input from mossy fibers andproject to the Purkinje cells.

Purkinje cells. The Purkinje cell is one of the most striking cell types in the mammalianbrain. Its apical dendrites form a large fan of finely branched processes. Remarkably, this

dendritic tree is almost two-dimensional; looked at from the side, the dendritic tree is flat and

almost dimensionless. Moreover, all Purkinje cells are oriented in parallel. This arrangement

has important functional considerations, as we shall see below.

Other cell types. In addition to the major cell types (granule cells and Purkinje cells),the cerebellar cortex also contains various interneuron types, including the Golgi cell, the basketcell, and the stellate cell.

Connectivity. The cerebellar cortex has a relatively simple, stereotyped connectivitypattern that is identical throughout the whole structure. Figure 5 illustrates a simplified diagram

of the connectivity of the cerebellum. Cerebellar input can be divided into two distinct classes.


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(1) Mossy fibers originate in the pontine nuclei, the spinal cord, the brainstem reticularformation, and the vestibular nuclei, and they make excitatory projections onto the cerebellar

nuclei and onto granule cells in the cerebellar cortex. They are called mossy fibers because of

the tufted appearance of their synaptic contacts with granule cells. There is a large degree ofdivergence in the mossy fiber-granule cell connection, as each mossy fiber innervates hundreds

of granule cells. The granule cells send axons up toward the cortical s

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